Associations between viremia with GB Virus C (GBV-C) and improved outcomes in established Human Immunodeficiency Virus (HIV) infection have been recently described. This research proposal examines GBV-C and HIV interactions in several ways, and, more broadly, is designed to provide the educational training and research experience necessary for a successful career in academic HIV clinical epidemiology. The proposal has three Specific Aims: Specific Aim 1: To evaluate the effect of GBV-C viremia on HIV acquisition risk. This specific aim hypothesizes that viremia with GBV-C decreases HIV acquisition risk. This hypothesis will be tested using a case-control design nested among the 4892 HIV negative individuals in the former Vaccine Preparedness Study (VPS) Uninfected Participant Cohort (UPC). The primary analysis will compare the 90 individuals in the UPC cohort who acquired HIV over the 18-month follow-up (cases) with 360 individuals (matched for duration of follow-up) who did not (controls) with respect to the proportion of the two groups with GBV-C viremia at the last visit prior to the cases' HIV acquisition. Sub-analyses will examine for a dose-response relationship of quantity and duration of GBV-C viremia on HIV acquisition risk. Specific Aim 2: To examine the effect of GBV-C viremia on HIV viral load set point. This specific aim will use a retrospective cohort design to test the hypothesis that GBV-C viral load lowers HIV viral load set point. The cohort will be comprised of all individuals who acquired HIV over VPS follow-up and who entered into a prospective cohort of early HIV (n=74), comparing those with GBV-C viremia and those without it with respect to HIV viral load set point. Sub-analysis will examine for a dose-response effect. Specific Aim 3: To examine the effect of GBV-C viremia on risk of HIV viral load breakthrough in a cohort of HIV-infected individuals virologically suppressed on HAART. This aim will be examined using a cohort study with GBV-C viremia at baseline as the exposure and viral load breakthrough as the outcome. Analysis will examine effect of GBV-C viremia on time to virologic breakthrough.